U.S. scientists fix disease genes in human embryos for 1st time

For the first time, scientists working in a U.S. lab have used gene editing to correct a disease-causing mutation in viable human embryos, according to scientific paper published Wednesday.

The work, reported in Nature, could be a step toward genetically modified babies. But the altered embryos created in the study were quickly destroyed and never intended to be implanted in a woman — a step that would be illegal under current regulations in the United States and many other countries.

Still, the experiment moves the idea of tinkering with genes before birth “from future fantasy to the world of possibility,” said Peter Braude, an emeritus professor of obstetrics and gynecology at King’s College London.

Safety and ethical questions remain, Braude and other experts not involved in the research said. And the technique has not been perfected enough to warrant moving forward.

“We still have room to improve,” said Shoukhrat Mitalipov, a researcher at Oregon Health & Science University (OHSU), Portland and lead author of the paper.

Here’s what Mitalipov and his colleagues, including scientists in the United States, South Korea and China, did:

• They recruited several healthy egg donors and one sperm donor who carried a gene for a common a heart condition called hypertrophic cardiomyopathy. The disease can cause heart failure and sudden death in unsuspecting adults. Under normal conditions, half of the man’s children would inherit the gene, the disease and the risk for passing it on.

• They fertilized the eggs with the man’s sperm. At the same time, the eggs were injected with gene editing tools. The tools, called CRISPR, included an enzyme primed to target and snip out the bad gene. The hope was the embryos would then repair the cuts with healthy versions.

• They found that 42 out of the 58 embryos (72.4%) were free of the disease-causing gene, a clear improvement over the expected 50%. Also, the repaired embryos appeared free of unintended changes, such as misplaced gene cuts or a mish-mash of healthy and unhealthy versions of the target gene. Such worrisome changes were found in earlier, smaller Chinese experiments.

• And they found one surprise: the embryos repaired themselves with DNA from the healthy egg, not a synthetic snippet provided by the researchers. That could limit the use of the method for introducing any sort of “designer” gene.

The technique would need to approach 100% effectiveness to be ready for clinical trials aimed at producing pregnancies, Mitalipov said. But, he said, the ultimate goal would be eliminating inherited risks for everything from cystic fibrosis to breast cancer.

Prospective parents can already look for and eliminate known disease genes by going through in vitro fertilization and having the resulting embryos screened for the genes. One advantage of gene editing is that it might reduce the number of IVF cycles a couple would need to get healthy, unaffected embryos, said study co-author Paula Amato, an associate professor of obstetrics and gynecology at OHSU.

Embryonic gene editing should move forward “only for compelling reasons and under strict oversight,” ethics experts said in a recent report from National Academy of Sciences and the National Academy of Medicine. The report said if the technology cannot be legally harnessed to prevent more questionable uses — such as the creation of so-called “designer babies” with desirable traits — it should remain off limits.

“There are still a lot of safety issues, a lot of legal and ethical issues,” even in medical uses, said Michael Werner, executive director of the Alliance for Regenerative Medicine in Washington, D.C. The group promotes the use of gene therapy to treat diseases, but has drawn a line at treating embryos.

“You are talking about permanently changing the genome of a person without their consent,” Werner said. “That’s an ethical question even if the technical challenges and safety get worked out.”